Additional file 1: of Measuring subjective well-being from a multidimensional and temporal perspective: Italian adaptation of the I COPPE scale

I COPPE Scale Italian Adaptation. (DOCX 337 kb

Epidemiology of CKD Regression in Patients under Nephrology Care

<div><p>Chronic Kidney Disease (CKD) regression is considered as an infrequent renal outcome, limited to early stages, and associated with higher mortality. However, prevalence, prognosis and the clinical correlates of CKD regression remain undefined in the setting of nephrology care. This is a multicenter prospective study in 1418 patients with established CKD (eGFR: 60–15 ml/min/1.73m²) under nephrology care in 47 outpatient clinics in Italy from a least one year. We defined CKD regressors as a ΔGFR ≥0 ml/min/1.73 m²/year. ΔGFR was estimated as the absolute difference between eGFR measured at baseline and at follow up visit after 18–24 months, respectively. Outcomes were End Stage Renal Disease (ESRD) and overall-causes Mortality.391 patients (27.6%) were identified as regressors as they showed an eGFR increase between the baseline visit in the renal clinic and the follow up visit. In multivariate regression analyses the regressor status was not associated with CKD stage. Low proteinuria was the main factor associated with CKD regression, accounting <i>per se</i> for 48% of the likelihood of this outcome. Lower systolic blood pressure, higher BMI and absence of autosomal polycystic disease (PKD) were additional predictors of CKD regression. In regressors, ESRD risk was 72% lower (HR: 0.28; 95% CI 0.14–0.57; p<0.0001) while mortality risk did not differ from that in non-regressors (HR: 1.16; 95% CI 0.73–1.83; p = 0.540). Spline models showed that the reduction of ESRD risk associated with positive ΔGFR was attenuated in advanced CKD stage. CKD regression occurs in about one-fourth patients receiving renal care in nephrology units and correlates with low proteinuria, BP and the absence of PKD. This condition portends better renal prognosis, mostly in earlier CKD stages, with no excess risk for mortality.</p></div

Cox analysis estimating the adjusted risk for ESRD and all-causes death of patients on the basis of regressor status and eGFR levels at the follow up visit.

<p>Analysis is adjusted for age, gender, diabetes, cardiovascular diseases, BMI, Systolic Blood Pressure, serum levels of phosphate, hemoglobin, uric acid, cholesterol and 24h proteinuria measured at follow up visit.</p><p>Cox analysis estimating the adjusted risk for ESRD and all-causes death of patients on the basis of regressor status and eGFR levels at the follow up visit.</p

Restricted cubic splines to evaluate the non-linear relationship of eGFR change with ESRD at each GFR level: above 45 ml/min/1.73 m² (top), between 30 and 45 ml/min/1.73 m² (middle) and below 30 ml/min/1.73 m² (bottom).

<p>The reference for the three GFR strata is 0 ml/min/1.73m² when ‎GFR level >45 ml/min/1.73 m² (top). Spline model is adjusted for age, gender, diabetes, BMI, previous CV disease, smoking, systolic BP, uric acid, hemoglobin, phosphate, cholesterol and 24h proteinuria measured at the follow up visit.</p

Main demographic, clinical and therapeutic features of patients stratified by regressor status.

<p>Data are mean±SD, percent or median (IQR).</p><p>*delta eGFR was calculated in 1307 patients due to the exclusion of 111 patients who developed ESRD between baseline and follow up visit.</p><p>** delta eGFR was calculated in 916 patients due to the exclusion of 111 patients who developed ESRD between baseline and follow up visit.</p><p>Abbreviations: BMI, body mass index; CVD, cardiovascular disease; eGFR, glomerular filtration rate estimated by the 4-variable MDRD equation; PKD, polycystic kidney disease; BP, blood pressure. ACEi, Angiotensin converting enzyme inhibitor; ARB, Angiotensin II receptor blocker; ESA, erythropoiesis stimulating agents.</p><p>Main demographic, clinical and therapeutic features of patients stratified by regressor status.</p

Logistic regression analysis estimating factors associated with the probability of being regressor and estimated contribution of each determinant to model fit (% R² reduction).

<p>*Non linear effect (p<0.0001) as shown in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0140138#pone.0140138.g002" target="_blank">Fig 2</a>.</p><p>Abbreviations: BMI, body mass index; CV, cardiovascular; ADPKD, autosomal dominant polycystic kidney disease; CKD, Chronic Kidney Disease; BP, blood pressure. ACEi, Angiotensin converting enzyme inhibitor; ARB, Angiotensin II receptor blocker; ESA, erythropoiesis stimulating agents.</p><p>Logistic regression analysis estimating factors associated with the probability of being regressor and estimated contribution of each determinant to model fit (% R² reduction).</p

Selection algorithm of patients.

<p>Selection algorithm of patients.</p

Differences of clinical and laboratory parameters between baseline and follow up visit in regressors and non-regressors.

<p>*P<0.0001 vs. regressors;</p><p>^# p<0.001 vs. regressors;</p><p>^§p<0.05 vs. regressors.</p><p>Abbreviations: FU: Follow up; eGFR, glomerular filtration rate estimated by the 4-variable MDRD equation; BP, blood pressure.</p><p>Differences of clinical and laboratory parameters between baseline and follow up visit in regressors and non-regressors.</p

Efficacy and safety of sparsentan versus irbesartan in patients with IgA nephropathy (PROTECT): 2-year results from a randomised, active-controlled, phase 3 trial

Background Sparsentan, a novel, non-immunosuppressive, single-molecule, dual endothelin angiotensin receptor antagonist, significantly reduced proteinuria versus irbesartan, an angiotensin II receptor blocker, at 36 weeks (primary endpoint) in patients with immunoglobulin A nephropathy in the phase 3 PROTECT trial's previously reported interim analysis. Here, we report kidney function and outcomes over 110 weeks from the double-blind final analysis. Methods PROTECT, a double-blind, randomised, active-controlled, phase 3 study, was done across 134 clinical practice sites in 18 countries throughout the Americas, Asia, and Europe. Patients aged 18 years or older with biopsy-proven primary IgA nephropathy and proteinuria of at least 1·0 g per day despite maximised renin–angiotensin system inhibition for at least 12 weeks were randomly assigned (1:1) to receive sparsentan (target dose 400 mg oral sparsentan once daily) or irbesartan (target dose 300 mg oral irbesartan once daily) based on a permuted-block randomisation method. The primary endpoint was proteinuria change between treatment groups at 36 weeks. Secondary endpoints included rate of change (slope) of the estimated glomerular filtration rate (eGFR), changes in proteinuria, a composite of kidney failure (confirmed 40% eGFR reduction, end-stage kidney disease, or all-cause mortality), and safety and tolerability up to 110 weeks from randomisation. Secondary efficacy outcomes were assessed in the full analysis set and safety was assessed in the safety set, both of which were defined as all patients who were randomly assigned and received at least one dose of randomly assigned study drug. This trial is registered with ClinicalTrials.gov, NCT03762850. Findings Between Dec 20, 2018, and May 26, 2021, 203 patients were randomly assigned to the sparsentan group and 203 to the irbesartan group. One patient from each group did not receive the study drug and was excluded from the efficacy and safety analyses (282 [70%] of 404 included patients were male and 272 [67%] were White) . Patients in the sparsentan group had a slower rate of eGFR decline than those in the irbesartan group. eGFR chronic 2-year slope (weeks 6–110) was −2·7 mL/min per 1·73 m2 per year versus −3·8 mL/min per 1·73 m2 per year (difference 1·1 mL/min per 1·73 m2 per year, 95% CI 0·1 to 2·1; p=0·037); total 2-year slope (day 1–week 110) was −2·9 mL/min per 1·73 m2 per year versus −3·9 mL/min per 1·73 m2 per year (difference 1·0 mL/min per 1·73 m2 per year, 95% CI −0·03 to 1·94; p=0·058). The significant reduction in proteinuria at 36 weeks with sparsentan was maintained throughout the study period; at 110 weeks, proteinuria, as determined by the change from baseline in urine protein-to-creatinine ratio, was 40% lower in the sparsentan group than in the irbesartan group (−42·8%, 95% CI −49·8 to −35·0, with sparsentan versus −4·4%, −15·8 to 8·7, with irbesartan; geometric least-squares mean ratio 0·60, 95% CI 0·50 to 0·72). The composite kidney failure endpoint was reached by 18 (9%) of 202 patients in the sparsentan group versus 26 (13%) of 202 patients in the irbesartan group (relative risk 0·7, 95% CI 0·4 to 1·2). Treatment-emergent adverse events were well balanced between sparsentan and irbesartan, with no new safety signals. Interpretation Over 110 weeks, treatment with sparsentan versus maximally titrated irbesartan in patients with IgA nephropathy resulted in significant reductions in proteinuria and preservation of kidney function.</p